Role of hippocampal metabotropic glutamate receptor 5 (mGluR5) in stress-induced response : physiological and behavioral analyses

Abstract

An individual’s behavior is generally based on genetic blueprint and previous experiences. A coping strategy, affected by personal interpretation of past events, can be determined by behavioral controllability of stress. In this study, I investigated the role of mGluR5 in stress-induced physiological and behavioral responses by using two different behavioral models; the helplessness paradigm and the restraint stress model. An increased or decreased mGluR5 expression was found in the hippocampus of the repetitive exposure to the uncontrollable stressor. An increased mGluR5 protein expression level is accompanied by the helplessness (HL) (+) behavior, a decreased EEG theta power and an increased blood corticosterone concentration, suggesting the negative adaptation to the stressor. In contrast, a decreased mGluR5 protein expression level is accompanied by the HL (-) behavior, no changed EEG and no changed corticosterone level, suggesting the positive adaptation to the stressor.Moreover, the increased mGluR5 protein expression level is positively related to the increased mGluR5 mRNA level, no changed DNA methyltransferase (DNMT) 3a mRNA level, and a decreased methylation site in the CpG island of the mGluR5 gene, while decreased mGluR5 protein expression level is positively related to the decreased mGluR5 mRNA level, the increased DNMT 3a mRNA level, and increased DNA methylation sites of the mGluR5 gene.Thus these results suggest that mGluR5, one of the candidate molecules modulating specific forms of memory, played a critical role in the development of controllability-dependent stress coping strategies, and epigenetic modulation of mGluR5 gene is involved in the adaptation mechanism.